The thymus is involved in immunologic and endocrinologic homeostasis of the body. See Besedovsky, et al. Nature 249:356-361 (1974). The importance of the thymus gland in the development and senescence of immunological competence in mammals now is generally accepted. Various factors of the thymus gland are recognized to modulate the levels of sex steroids which in turn can cause spontaneous and experimentally induced autoimmune diseases and alter the immune response during pregnancy. See Oates, et al., Trends Pharmacol. Sci. 5:347 (1984). Several humoral factors possessing hormone-like activity have been isolated and characterized from the thymus or its extracts. See e.g., Goldstein, et al. Proc. Natl. Acad. Sci. 74:725-729 (1977). Factors which have been isolated include prothymosin-.alpha. (ProT.alpha.), thymosin-.alpha..sub.1 (T.alpha..sub.1) and thymosin-.beta..sub.4 (T.beta..sub.4). T.alpha..sub.1 and T.beta..sub.4 have been sequenced and synthesized. The sequence of T.alpha..sub.1 is shown, for example, in U.S. Pat. No. 4,079,127 (Goldstein et al.). The sequence of T.beta..sub.4 is provided in U.S. Pat. No. 4,297,276 (Goldstein, et al.).
The presence of T.alpha..sub.1 in human seminal plasma and in human follicular fluid has been reported. See Naz et al., Int. J. Fertil. 32:375 (1987), incorporated herein by reference. Naz et al. reported that there was a correlation between the amount of T.alpha..sub.1 in the seminal plasma and sperm counts and semen volume and that levels were significantly lower in males with defective sperm function.
Fertilization is a complex process requiring the spermatozoa to undergo a cascade of events before fusing with the egg plasma membrane. This chain of events includes capacitation of the sperm binding to the zona pellucida, acrosome reaction, and penetration through the zona pellucida, all as described in Naz et al., Current Opin. Immunol. 2:748-751 (1990). Capacitation is a physiological process that a mammalian sperm cell must undergo before it can fertilize an oocyte.
Infertility remains a problem for a substantial portion of the population. Cumulative data indicate that as many as one in four married couples in the United States who wish to have children have difficulty in conceiving a child. A number of techniques, such as artificial insemination, micromanipulation of the gametes and in vitro fertilization, have been developed in recent years in efforts to overcome some of the causes of the problem. Many of these techniques are quite expensive, however, and the success rates have been low. Accordingly, there exists a substantial need for compositions and methods useful in the treatment of infertility.